We plan to continue studying the initial steps in the interaction between blood platelets and their aggregants. We shall concentrate on the effect of thrombin, adenosine diphosphate, collagen and epinephrine on the platelet membrane potential, platelet membrane fluidify, platelet membrane permeability to cations and on the intraplatelet concentrations of H ion and Ca ions. The effect of platelet aggregation perturbants such as aspirin, indomethacin, and some general anaesthetics on these parameters of platelet response will also be evaluated. The identification and isolation of the platelet receptor for thrombin, and of the receptor assembly recognizing collagen, have been accomplished; composition and conformation remain to be determined as do the detailed effects of binding to the receptor, i.e., the subsequent steps in the platelet reaction. The methods to be used in these studies include: spectrophotometry (to measure changes in intraplatelet concentrations of Ca ion and H ion), spectrofluorimetry (to measure platelet membrane potentials, membrane fluidities, intraplatelet pH), turbimetry (to measure collagen fibril formation), chemical modification (to design photoreactive aggregant analogues), flame photometry (to measure K ion and Na ion concentrations), as well as the usual isotope counting, chromatographic, electrophoretic and centrifugation techniques. By studying the early steps in the response of normal platelets to their aggregation stimuli we hope to develop a better understanding of the mechanism by which this response eventually leads to platelet release and aggregation. This knowledge will then allow us to evaluate the changes in platelet response brought about by disease, trauma, or congenital defects.